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Characterizing the Impact of Chitosan on the Nucleation and Crystal Growth of Ritonavir from Supersaturated Solutions

The addition of polymeric materials is often used to delay nucleation or crystal growth and maintain the high supersaturation of amorphous drugs. Therefore, this study aimed to investigate the impact of chitosan on the supersaturation behavior of drugs with a low recrystallization tendency and eluci...

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Autores principales: Budiman, Arif, Kalina, Kalina, Aristawidya, Levina, Shofwan, Adnan Aly Al, Rusdin, Agus, Aulifa, Diah Lia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10007235/
https://www.ncbi.nlm.nih.gov/pubmed/36904523
http://dx.doi.org/10.3390/polym15051282
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author Budiman, Arif
Kalina, Kalina
Aristawidya, Levina
Shofwan, Adnan Aly Al
Rusdin, Agus
Aulifa, Diah Lia
author_facet Budiman, Arif
Kalina, Kalina
Aristawidya, Levina
Shofwan, Adnan Aly Al
Rusdin, Agus
Aulifa, Diah Lia
author_sort Budiman, Arif
collection PubMed
description The addition of polymeric materials is often used to delay nucleation or crystal growth and maintain the high supersaturation of amorphous drugs. Therefore, this study aimed to investigate the impact of chitosan on the supersaturation behavior of drugs with a low recrystallization tendency and elucidate the mechanism of its crystallization inhibition in an aqueous solution. It was carried out using ritonavir (RTV) as a model of poorly water-soluble drugs categorized as class III of Taylor’s classification, while chitosan was used as a polymer, and hypromellose (HPMC) was used for comparison. The inhibition of the nucleation and crystal growth of RTV by chitosan was examined by measuring the induction time. The interactions of RTV with chitosan and HPMC were evaluated by NMR measurements, FT-IR, and an in silico analysis. The results showed that the solubilities of amorphous RTV with and without HPMC were quite similar, while the amorphous solubility was significantly increased by the chitosan addition due to the solubilization effect. In the absence of the polymer, RTV started to precipitate after 30 min, indicating that it is a slow crystallizer. Chitosan and HPMC effectively inhibited the nucleation of RTV, as reflected by a 48–64-fold enhancement in the induction time. Furthermore, NMR, FT-IR, and in silico analysis demonstrated that the hydrogen bond interaction between the amine group of RTV and a proton of chitosan, as well as the carbonyl group of RTV and a proton of HPMC, was observed. This indicated that the hydrogen bond interaction between RTV and chitosan as well as HPMC can contribute to the crystallization inhibition and maintenance of RTV in a supersaturated state. Therefore, the addition of chitosan can delay nucleation, which is crucial for stabilizing supersaturated drug solutions, specifically for a drug with a low crystallization tendency.
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spelling pubmed-100072352023-03-12 Characterizing the Impact of Chitosan on the Nucleation and Crystal Growth of Ritonavir from Supersaturated Solutions Budiman, Arif Kalina, Kalina Aristawidya, Levina Shofwan, Adnan Aly Al Rusdin, Agus Aulifa, Diah Lia Polymers (Basel) Article The addition of polymeric materials is often used to delay nucleation or crystal growth and maintain the high supersaturation of amorphous drugs. Therefore, this study aimed to investigate the impact of chitosan on the supersaturation behavior of drugs with a low recrystallization tendency and elucidate the mechanism of its crystallization inhibition in an aqueous solution. It was carried out using ritonavir (RTV) as a model of poorly water-soluble drugs categorized as class III of Taylor’s classification, while chitosan was used as a polymer, and hypromellose (HPMC) was used for comparison. The inhibition of the nucleation and crystal growth of RTV by chitosan was examined by measuring the induction time. The interactions of RTV with chitosan and HPMC were evaluated by NMR measurements, FT-IR, and an in silico analysis. The results showed that the solubilities of amorphous RTV with and without HPMC were quite similar, while the amorphous solubility was significantly increased by the chitosan addition due to the solubilization effect. In the absence of the polymer, RTV started to precipitate after 30 min, indicating that it is a slow crystallizer. Chitosan and HPMC effectively inhibited the nucleation of RTV, as reflected by a 48–64-fold enhancement in the induction time. Furthermore, NMR, FT-IR, and in silico analysis demonstrated that the hydrogen bond interaction between the amine group of RTV and a proton of chitosan, as well as the carbonyl group of RTV and a proton of HPMC, was observed. This indicated that the hydrogen bond interaction between RTV and chitosan as well as HPMC can contribute to the crystallization inhibition and maintenance of RTV in a supersaturated state. Therefore, the addition of chitosan can delay nucleation, which is crucial for stabilizing supersaturated drug solutions, specifically for a drug with a low crystallization tendency. MDPI 2023-03-03 /pmc/articles/PMC10007235/ /pubmed/36904523 http://dx.doi.org/10.3390/polym15051282 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Budiman, Arif
Kalina, Kalina
Aristawidya, Levina
Shofwan, Adnan Aly Al
Rusdin, Agus
Aulifa, Diah Lia
Characterizing the Impact of Chitosan on the Nucleation and Crystal Growth of Ritonavir from Supersaturated Solutions
title Characterizing the Impact of Chitosan on the Nucleation and Crystal Growth of Ritonavir from Supersaturated Solutions
title_full Characterizing the Impact of Chitosan on the Nucleation and Crystal Growth of Ritonavir from Supersaturated Solutions
title_fullStr Characterizing the Impact of Chitosan on the Nucleation and Crystal Growth of Ritonavir from Supersaturated Solutions
title_full_unstemmed Characterizing the Impact of Chitosan on the Nucleation and Crystal Growth of Ritonavir from Supersaturated Solutions
title_short Characterizing the Impact of Chitosan on the Nucleation and Crystal Growth of Ritonavir from Supersaturated Solutions
title_sort characterizing the impact of chitosan on the nucleation and crystal growth of ritonavir from supersaturated solutions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10007235/
https://www.ncbi.nlm.nih.gov/pubmed/36904523
http://dx.doi.org/10.3390/polym15051282
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